Melasma is a common, persistent disorder of hyperpigmented facial skin predominantly attributed to ultraviolet light exposure, hormonal influences, and genetic predisposition. This double-blind, placebo-controlled, randomized clinical trial was conducted to assess the efficacy and tolerance of a multimodality night cream when used over a course of 24 weeks followed by a four-week regression in female subjects with moderate to severe melasma, presence of solar lentigines, and periocular lines and wrinkles. Subjects were randomized into one of two groups: Cell 1 received Trifecting Night Cream (Envy Medical, Long Beach, California) 1.0 and Cell 2 did not. All subjects were supplied with a two-product regimen comprising a cleanser and sunscreen to use during the trial. Clinical grading, tolerability assessments, and Chroma Meter measurements (Konica Minolta, Tokyo, Japan) were performed at baseline and at Weeks 8, 16, 24, and 28 (regression). Standardized digital photographs were taken and self-assessment questionnaires were completed. Twenty-five subjects completed the 28-week study, with 14 subjects in Cell 1 and 11 subjects in Cell 2. Subjects in both groups showed improvements in facial conditions. Cell 1 outperformed Cell 2 in improving fine lines, solar lentigines, and melasma conditions. These improvements were sustained during regression period. Trifecting Night Cream 1.0, is effective for the treatment of moderate to severe melasma, solar lentigines, and periocular lines and wrinkles over 24 weeks of usage, with its benefits sustained for at least four weeks after treatment.